Structures and Functions of Snake Venom Metalloproteinases (SVMP) from Protobothrops venom Collected in Japan

Abstract

Snake venom metalloproteinases (SVMP) are widely distributed among the venoms of Crotalinae and Viperidae, and are organized into three classes (P-I, P-II and P-III) according to their size and domain structure. P-I SVMP are the smallest SVMP, as they only have a metalloproteinase (M) domain. P-II SVMP contain a disintegrin-like (D) domain, which is connected by a short spacer region to the carboxyl terminus of the M domain. P-III SVMP contain a cysteine-rich (C) domain, which is attached to the carboxyl terminus of the D domain. Some SVMP exhibit hemorrhagic activity, whereas others do not. In addition, SVMP display fibrinolytic/fibrinogenolytic (FL) activity, and the physiological functions of SVMP are controlled by their structures. Furthermore, these proteinases also demonstrate fibrinogenolytic and proteolytic activity against synthetic substrates for matrix metalloproteinases and ADAM (a disintegrin and metalloproteinase). This article describes the structures and FL, hemorrhagic, and platelet aggregation-inhibiting activity of SVMP derived from Protobothrops snake venom that was collected in Japan.

Comprehensive Snake Venomics of the Okinawa Habu Pit Viper, Protobothrops flavoviridis, by Complementary Mass Spectrometry-Guided Approaches

“…The main compound of the fraction 4 is the svMP-i pEKW, while the pEQW containing fraction 7/8 is similarly potent. According to these results, the P. flavoviridis venom, svMP-is, exhibits remarkable effects on SH-SY5Y cells, while, until now, only the correlating svMP of most Protobothrops venoms were known to have an important role in envenomation-related pathologies [ 46 , 64 ]. Regarding the identified families, PLA 2s , as the main venom part, are most active in fraction 15 (PLA 2 , 2.2 µg/mL), in combination with a CTF-II-like disintegrin, against neuroblastoma cells.…”

Atrase A, a P-III class metalloproteinase purified from cobra venom, exhibits potent anticoagulant activity by inhibiting coagulation pathway and activating the fibrinolytic system

“…The current study revealed that SVMPs exhibit different activities such as hydrolyzing of fibrinogen or fibrin, action of thrombin or inhibition of platelet aggregation [ 35 ]. For example, the P–I class BnP1 from B. neuwiedi venom and the P-III class Jararhagin from Bothrops jararaca venom directly hydrolyze fibrinogen and fibrin [ [36] , [37] , [38] ], HF3 and bothropasin from Bothrops jararaca inhibit platelet aggregation [ 39 ], Mocarhagin isolated from Naja venom inhibits platelet aggregation by cleaving GPIb [ 15 ], Berythractivase from Bothrops erythromelas , which acts as a thrombinogen activator [ 40 ].…”

Comprehensive snake venomics of the Okinawa Habu pit viper, Protobothrops flavoviridis, by complementary mass spectrometry-guided approaches

“…The main compound of the most active fraction 6 is the svMP-i pENW, while the pEQW containing fraction 7 less cell toxic (4.6 μg/mL). According to this cytotoxicity results, the P. flavoviridis venom svMP-i exhibits remarkable effects on SH-SY5Y cells, while until now only the correlating svMP of most Protobothrops venoms were known for their important role in envenomation-related pathologies [46,60]. Regarding the identified families, PLA2s as main venom part are most active in fractionss 15 (PLA-N(O), 2.2 µg/mL) and 14 (PLA2 BP-I/II, 4.0 µg/mL), against neuroblastoma cells.…”